Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
Instituto de Investigación en Biomoléculas (INBIO), Universidad de Cádiz, Puerto Real, 11510 Cádiz, Spain.
Mar Drugs. 2022 Jan 18;20(2):84. doi: 10.3390/md20020084.
Marine microorganisms have proven to be a source of new natural products with a wide spectrum of biological activities relevant in different industrial sectors. The ever-increasing number of sequenced microbial genomes has highlighted a discrepancy between the number of gene clusters potentially encoding the production of natural products and the actual number of chemically characterized metabolites for a given microorganism. Homologous and heterologous expression of these biosynthetic genes, which are often silent under experimental laboratory culture conditions, may lead to the discovery of new cryptic natural products of medical and biotechnological interest. Several new genetic and cultivation-based strategies have been developed to meet this challenge. The OSMAC approach (one strain-many compounds), based on modification of growth conditions, has proven to be a powerful strategy for the discovery of new cryptic natural products. As a direct extension of this approach, the addition of chemical elicitors or epigenetic modifiers have also been used to activate silent genes. This review looks at the structures and biological activities of new cryptic metabolites from marine-derived microorganisms obtained using the OSMAC approach, the addition of chemical elicitors, and enzymatic inhibitors and epigenetic modifiers. It covers works published up to June 2021.
海洋微生物已被证明是具有广泛生物活性的新型天然产物的来源，这些产物在不同的工业领域都具有重要作用。越来越多的微生物基因组测序结果表明，潜在能够编码天然产物生产的基因簇数量与给定微生物中经化学表征的代谢物数量之间存在差异。这些生物合成基因的同源和异源表达（在实验实验室培养条件下通常处于沉默状态）可能会发现具有医学和生物技术应用价值的新型隐藏天然产物。为了应对这一挑战，已经开发了几种新的基于遗传和培养的策略。基于生长条件修饰的 OSMAC 方法（一种菌株多种化合物）已被证明是发现新型隐藏天然产物的有力策略。作为该方法的直接延伸，还添加了化学诱导剂或表观遗传修饰剂来激活沉默基因。本综述着眼于使用 OSMAC 方法、添加化学诱导剂以及酶抑制剂和表观遗传修饰剂获得的海洋来源微生物中新的隐藏代谢物的结构和生物活性。涵盖了截至 2021 年 6 月发表的作品。
